Tpl2 transgenic knockout mice

Abstract

The present invention is directed to animal having functionally disrupted endogenous Tpl2. These animals are resistant to Lps induced endotoxin shock and TNFalpha-mentioned inflammatory disease. A method of identifying Tpl2 specific inhibitors of endotoxin shock or antagonists to inflammation on and a method of treating or preventing TNFalpha-mediated inflammatory diseases and Lps induced endotoxin shock in animals are also within the scope of this invention. The present invention is also directed to Tpl2 encoding nucleic acid molecules (SEQ ID NOS: 1 and 3) and polypeptides (SEQ ID NOS: 2 and 4) encoded by such molecules.

What is claimed is:  
     
       1. A transgenic mouse whose genome comprises a homozygous inactivated Tpl2 gene, wherein said inactivation is by the insertion of an exogenous sequence into said gene or by replacement of part of the endogenous Tpl2 gene with an exogenous sequence and wherein said mouse does not produce functional Tpl2 and exhibits a phenotype of resistance to LPS induced endotoxin shock or TNFα-mediated inflammatory disease. 
     
     
       2. The transgenic mouse of  claim 1 , wherein said mouse exhibits a phenotype of resistance to LPS induced endotoxin shock. 
     
     
       3. The transgenic mouse of  claim 1 , wherein said mouse exhibits a phenotype of resistance to TNFα-mediated inflammation. 
     
     
       4. Spleen cells or macrophages isolated from the transgenic mouse of  claim 1 . 
     
     
       5. A transgenic mouse whose genome comprises a homozygous disruption of the endogenous Tpl-2 gene, wherein said mouse does not produce functional Tpl2 and exhibits a phenotype of resistance to LPS induced endotoxin shock or TNFα-mediated inflammatory disease. 
     
     
       6. The transgenic mouse of  claim 5 , wherein said mouse exhibits a phenotype of resistance to LPS induced endotoxin shock or TNFα-mediated inflammatory disease. 
     
     
       7. The transgenic mouse of  claim 5 , wherein said mouse exhibits a phenotype of resistance to TNFα-mediated inflammatory disease. 
     
     
       8. Spleen cells or macrophages isolated from the transgenic mouse of  claim 5 .